Many cancers originate and progress by accumulating mutations in one or more genes. Such mutations which result in cancer formation can be in proto-oncogenes or in tumor supressor genes. Mutations in tumor supressor genes result in loss of function, and therefore act in a recessive fashion to wild-type genes. Oncogenes, in contrast, act in dominant fashion to wild-type alleles and, therefore, are not usually inherited through the germ lines. The tumor supressor genes, however, are found in inherited predispositions to cancer and are inherited as a dominant predisposition because of the high frequency of a second genetic event such as reduction in homozygosity[1].
Several tumor supressor genes have been identified. Examples include the Rb gene, which is involved in retinoblastoma and osteosarcoma; p53, which is involved in osteosarcoma and adrenocortical, breast and brain cancers; WT-1, which is involved in Wilms' tumor, nephroblastoma and neurofibromatosis; adenomatous polyposis coli (APC), which is involved in adenomatous polyposis; and deleted colorectal cancer (DCC), which is involved with a somatic mutation in the colon.
The negative regulation of cell growth is affected by tumor supressor proteins that regulate the cell cycle by different mechanisms[2]. The gene cloned and sequenced as described herein, p33.sup.IG1, represents a new tumor suppressor gene which is expressed in normal mammary epithelial cells, but expressed only at lower levels in several cancerous mammary epithelial cell lines.
Known applications of sequenced genes include use of the DNA sequence (or analogs thereof) or of RNA or amino acid sequences derived from these DNA sequences for diagnosis or treatment of the corresponding disease. Accordingly, p33.sup.IG1 is useful for the diagnosis and treatment of breast cancer.